Immunological basis for latency, recurrences and putative oncogenicity of herpes simplex virus.

The development of latency and recurrent infection after primary herpes simplex virus (H.S.V.) infection can be interpreted in terms of cell-mediated and antibody responses to virus-specific antigens and Fc receptors on the surface of the infected cells. Primary infection will induce immune responses to the virus, and antibody and cell-dependent cytotoxic mechanisms will kill most of the virus and virus-infected cells which are accessible to killer cells. H.S.V. will be sequestrated to the nerves and will migrate centripetally along the axons to the trigeminal or sensory ganglia. Latency in the trigeminal ganglion may be mediated by IgG antibodies binding to both H.S.V. antigens and Fc receptors. Derepression of the viral genome may be induced by factors which weaken the binding of antibodies to the antigen and Fc receptor; the virus will replicate and migrate centrifugally along the axon, to be shed at the nerve endings. In the presence of some defect in T lymphocytes, acting at the neuroepithelial junction, a recurrent herpetic lesion will be precipitated. There is some evidence that H.S.V. may be associated with squamous-cell carcinoma, and it is postulated that the enhanced cell-mediated and antibody responses to H.S.V. may destroy cells containing the viral genome but allow the emergence of an oncogenic genome. Double binding of the Fc receptor and H.S.V. antigen by IgG antibodies or immune complexes on the surface of carcinoma cells may prevent killing and allow these cells to proliferate into invasive tumours.